Medical Genetics Commons^™

Integrating Genetic Modifier Genotype With Serum Proteomics In Duchenne Muscular Dystrophy Clinical Trials Links Ltbp4 Genetic Modifier To Il-23/Cd93 Pathways In Muscle, Utkarsh J. Dang, Yuan Fang, Daniele Sabbatini, Elena Pegoraro, Luca Bello, Paula R. Clemens, Michela Guglieri, John Van Den Anker, Jesse Damsker, Laura Hagerty, Yetrib Hathout, Michael Ziemba, Lauren Morgenroth, Surajit Bhattacharya, Kanneboyina Nagaraju, Jyoti K. Jaiswal, Eric P. Hoffman

Mathematics & Statistics Faculty Publications

Genetic modifiers of Duchenne muscular dystrophy (DMD) that alter disease severity or response to therapy have been reported using natural history or registry data sets of older corticosteroid-treated patients. We tested associations of genetic modifiers on motor function outcomes in young (4 to <  7 years) steroid naïve clinical trial participants. Participants in clinical trials (VBP15-002/003 [n = 48]; VBP15-004 [n = 121]; DNA available for n = 110) were genotyped for eight published genetic modifier loci, and associations of genotypes with baseline motor function defined via an age-adjusted linear model. Corticosteroid drug response was modeled by genotype-stratified placebo vs. steroid treatment at 12- and 24-weeks posttreatment (mixed model for repeated measures). …

An Ensemble Classifier For Ordinal Outcomes In High-Dimensional Genomics Data, Heranga K. Rathnasekara, Sinjini Sikdar

Mathematics & Statistics Faculty Publications

Analysis of genomics data for predicting disease outcomes is a fast-growing field in medical research. There often exist categorical, specifically, ordinal outcomes that need to be predicted based on genomic profiles. This has led to recent development of some high-dimensional ordinal classification methods that can address the large dimensionality of the genomic covariate set. These high-dimensional ordinal models tend to vary widely in their performance depending on the data they are applied to and the evaluation criteria used. In this article, we outline an ensemble ordinal classifier that integrates different ordinal modeling approaches through bootstrap-based model evaluation, multi-metric performance assessment, …

Bortezomib And Vorinostat In Combination With Mitoxantrone, Dexamethasone, And Pegasparaginase During Induction And Reinduction For Infants With Acute Lymphoblastic Leukaemia: A Multicentre Single-Arm Phase 1/2 Study, Tanja A. Gruber, Sima Jeha, Rebecca J. Deyell, Victor Lewis, Bill H. Chang, Eric J. Lowe, Jamie Frediani, Catherine Vezina, Bruno Michon, Michael Richards, Erin H. Breese, Thai-Hoa Tran, Norman Lacayo, Christine Bolen, Sunil Desai, Jennifer L. Pauley, Minxuan Huang, Emily Ashcraft, Cheng Cheng, Kirk R. Schultz, Linda Stork, Krysta Schlis, Van T. Huynh, Nathan Gossai, Yoav H. Messinger, Henrique Bittencourt, Terzah M. Horton, Uma Athale, Duncan Stearns, Deborah Schiff, Paul S. Gaynon

Department of Pediatrics Faculty Publications

Background: Acute lymphoblastic leukaemia in infants remains a therapeutic challenge. In preclinical studies we previously identified bortezomib and vorinostat as active agents against KMT2A rearranged (KMT2Ar) leukaemia. The aim of this study was to determine the tolerability of incorporating bortezomib and vorinostat into an acute lymphoblastic leukaemia-chemotherapy backbone for newly diagnosed infants with acute lymphoblastic leukaemia both with and without KMT2Ar.

Methods: In this single-arm phase 1/2 study conducted at 18 hospitals in the USA and Canada, we enrolled patients aged 1 year or younger at the time of diagnosis with newly diagnosed acute lymphoblastic leukaemia or undifferentiated leukaemia (with …

35 Individuals With Huwe1-Related Neurodevelopmental Disorder And Suggested Clinical Evaluations, Mindy H. Li, Deziree L. Coleman, Kelsey Hogan, Danielle Luz, Lindsay Bhandari, Newell Belnap, Tiffany Busa, Charles Coutton, Klaus Dieterich, Svetlana Gorokhova, Clara Hildebrandt, Rachel Logan, Milena Mariani, Manuela Morleo, Vincenzo Nigro, John Pappas, Rachel Rabin, Kelly Schoch, Angelo Selicorni, Vandana Shashi, Rebecca Spillman, Jennifer Sullivan, Charlotte Tardy, Samantha A. Schrier Vergano, Brock Grill, Kristin Baranano

Department of Pediatrics Faculty Publications

HUWE1 (HECT, UBA, and WWE Domain Containing E3 Ubiquitin Protein Ligase1, OMIM 300697), located at Xp11.22, encodes a ubiquitin ligase that is highly conserved across species. Genetic variants in HUWE1 described in multiple independent studies cause X-linked intellectual disability, including in the patients identified by Juberg, Marsidi, and Brooks. This report describes 35 additional cases of individuals with variants in HUWE1 and suggested guidelines for clinical management. Our study includes several female cases, which have not been widely reported previously. Our findings confirm earlier reported clinical features including developmental delay, autism, hypotonia, short stature, and dysmorphic facial features as well …

Dysregulation Of Alternative Splicing Patterns In The Ovaries Of Reproductively Aged Mice, Adnan T. Alsamaraee, Vanessa L. Correll, Julius O. Nyalwidhe, Pavla Brachova, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Female reproductive aging is characterized by progressive deterioration of ovarian function, yet the molecular mechanisms driving these changes remain incompletely understood. Here, we used long-read direct RNA-sequencing to map transcript isoform changes in mouse ovaries across reproductive age. Comparing young and aged mice after controlled gonadotropin stimulation, we identified widespread alternative splicing changes, including shifts in exon usage, splice site selection, and transcript boundaries. Aged ovaries exhibited increased isoform diversity, favoring distal start and end sites, and a significant rise in exon skipping and intron retention events. Many of these age-biased splicing events altered open reading frames, introduced premature stop …

Inhibition Of Histone Demethylase Lsd1 Suppresses Cd47 Expression And Enhances Efficacy Of Cd47 Blockade In Breast Cancer, Fengjie Jiang, Yu Shen, Bing Li, Michael Henry, Nancy Davidson, Yi Huang

Department of Biomedical and Translational Sciences Faculty Publications

Background CD47 functions as a “don’t eat me” checkpoint, inhibiting macrophage-mediated phagocytosis in triple-negative breast cancer (TNBC). While anti-CD47 therapies can restore immune surveillance, their efficacy in TNBC is often limited by immune evasion and drug development challenges.

Methods We investigated the crosstalk between the histone demethylase lysine-specific demethylase 1 (LSD1) and CD47 signaling in TNBC using in silico datasets, isogenic cell lines, conditional BRCA1 knockout models, and syngeneic mouse models. Techniques such as immunohistochemistry, multiplex immunofluorescence, immunoprecipitation, protein ubiquitination, chromatin immunoprecipitation, chemotaxis, flow cytometry, and phagocytosis assays were employed to examine the epigenetic regulation of CD47 by LSD1 and …

Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Background/Aim: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

Materials and Methods: Phosphorus (32P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.

Results: A total of 35 out of the 588 genes were differentially expressed, with either log2 ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤−1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and 25 of these were significantly …

A Complete Diploid Human Genome Benchmark For Personalized Genomics, Nancy F. Hansen, Nathan Dwarshuis, Hyun Joo Ji, Arang Rhie, Hailey Loucks, Glennis A. Logsdon, Mitchell R. Vallger, Jessica M. Storer, Juhyun Kim, Eleni Adam, Nicolas Alternose, Dmitry Antipov, Mobin Asri, Sofia Barreira, Stephanie C. Bohaczuk, Andrey V. Bzikadze, Sara A. Carioscia, Andrew Carroll, Kuan-Hao Chao, Yanan Chu, Arun Das, Peter Ebert, Adam English, Mark Fleharty, Laura E. Fleming, Giulio Formenti, Andrea Guarracino, Gabrielle A. Hartley, Katharine Jenike, Jenna Kalleberg, Yu Kang, Robert King, Josipa Lipovac, Mira Mastoras, Matthew W. Mitchell, Shloka Negi, Nathan D. Olson, Keisuke K. Oshima, Luis F. Paulin, Brandon D. Pickett, David Porubsky, Jane Ranchalis, Desh Ranjan, Mikko Rautiainen, Harold Riethman, Robert D. Schnabel, Fritz J. Sedlazeck, Kishwar Shafin, Mile Sikic, Steven J. Solar, Alexander P. Sweeten, Winston Timp, Justin Wagner, Dongahn Yoo, Ying Zhou, Erik Garrison, Evan E. Eichler, Michaeel C. Schatz, Andrew B. Stergachis, Rachel J. O'Neill, Karen H. Miga, Steven L. Salzberg, Sergey Koren, Justin M. Zook, Adam M. Phillippy

School of Medical Diagnostics & Translational Sciences Publications

Human genome sequencing typically relies on mapping reads to a reference genome to call variants, but this approach introduces technical biases, excluding duplicated and structurally polymorphic regions of the genome. To overcome this, we present a telomere-to-telomere genome benchmark with near-perfect accuracy across 99.4% of the diploid HG002 genome. This benchmark adds 701.4 Mb of autosomal sequence and both sex chromosomes (216.8 Mb), which were absent from prior benchmarks. We annotated genes and repeats on both haplotypes, including 19,956 protein-coding genes on the maternal haplotype and 19,190 on the paternal haplotype, and developed new methods to measure the accuracy of …

Donor-Derived Cell-Free Dna In Antibody-Mediated Rejection: An Analysis Of The Surveillance Heartcare Outcomes Registry, Paul J. Kim, Amit H. Alam, Jeffrey J. Teuteberg, Kiran K. Khush, Sean P. Pinney, Richard K. Cheng, Amin Yehya, Jeremy Kobulnik, Kevin M. Pinney, Kris A. Oreschak, Christopher R. Ensor Pharmd, Steven Fan, Marcus A. Urey, Palak Shah, Shelley A. Hall

Department of Medicine Faculty Publications

Background

Donor-derived cell-free DNA (dd-cfDNA) has emerged as a biomarker for antibody-mediated rejection (AMR), but its performance characteristics have not been evaluated in a large contemporary heart transplant population.

Objectives

The study aimed to characterize the incidence and timing of biopsy-proven AMR and evaluate the performance characteristics of dd-cfDNA for AMR.

Methods

The authors included 2,240 subjects from the SHORE (Surveillance HeartCare Outcomes Registry) registry transplanted between 2017 and 2022 with verified biopsy, dd-cfDNA, echocardiographic, and donor-specific antibody (DSA) data. They evaluated the performance characteristics of dd-cfDNA for AMR and the incidence of AMR in different clinical contexts.

Results

AMR …

Acute Fatty Liver Of Pregnancy And Fetal Fatty Acid Oxidation Disorders: A Systematic Review, Dante Varotsis, Sarah Araji, Rebecca Horgan, Jennifer E. Powel, Rodney Mclaren Jr., Brian Kirmse, Mona Makhamreh, Huda B. Al-Kouatly

Department of Obstetrics & Gynecology Faculty Publications

OBJECTIVE:

To evaluate the association between maternal acute fatty liver of pregnancy (AFLP) and fetal fatty acid oxidation (FAO) disorders and to define the clinical and genetic characteristics of mothers with AFLP and their fetuses affected by FAO disorders, we performed a systematic literature review of all reported cases of AFLP that underwent genetic testing for FAO disorders.

DATA SOURCES:

We searched PubMed, Ovid MEDLINE, Cochrane Library, CINAHL (EBSCO), Scopus, and ClinicalTrials.gov. Terms included were related to AFLP and FAO testing.

METHODS OF STUDY SELECTION:

We conducted a systematic literature review from inception through May 18, 2025, to evaluate the …

A Cross-Sectional Study Investigating The Relationship Between The Fto Gene Polymorphism In Relation To Obesity Traits And Vitamin D Status In Adolescence, Ahmad Al-Serri, Rabeah A. Al-Temaimi, Abdullah Al-Taiar, Lemia Shaban, Reem Al-Sabah, Abdur Rahman, Ali H. Ziyab

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Background and Objective: Obesity affects 18%-25% of adolescents globally and represents a major public health challenge. Genetic factors contribute to obesity susceptibility, with the FTO gene variant rs9939609 consistently associated with obesity in adults; however, evidence in adolescents is limited. This study examined the association between FTO and obesity traits in adolescents and explored potential interactions with vitamin D status.

Methods: In this cross-sectional study, 509 adolescents aged 10-15 years were genotyped for FTO rs9939609. Obesity traits, including BMI, BMI z-score, and waist circumference, were assessed. Associations with genotype were analyzed using an additive genetic model, and potential interactions with …

Micrornas Regulated By Pregnancy Target Antiviral And Cancer Immunity Overlapping With The Hiv Interactome, Paula F. T. Cezar-De-Mello, Jonathan M. Dreyfuss, Pai-Lien Chen, Hidemi Yamamoto, Xiaoming Gao, Hui Pan, Charles Morrison, Gustavo F. Doncel, Robert L. Barbieri, Raina N. Fichorova

CONRAD Publications

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways …

From Screens To Stress: Public Health Implications Of Cancer Worry In A Digitally Connected World, Shreya Mathur, Ethan Burns, Michael Pokojovy, Tzu-Liang Bill Tseng, Sunil Mathur

Mathematics & Statistics Faculty Publications

Aims:

This study examines how digital information environments, genetic testing experiences, health behaviors, and psychological distress influence cancer-related worry among adults in the United States. It further considers the public health implications of elevated or reduced cancer worry for prevention and risk communication.

Methods:

Data were drawn from a nationally representative survey of 6,252 U.S. adults. Measures included reliance on social media for health decision-making, smoking status, history of genetic testing, and psychological distress. Multivariable analyses assessed associations between these factors and levels of cancer worry.

Results/Findings:

Reliance on social media for health decisions was associated with greater cancer worry, …

Chromnet: A Multi-Task Learning Framework For Cross-Cell Type Prediction Of 3d Chromatin Interactions Using Epigenetic Signals, Bin Wang, Shaokai Wang, Liqing Ding, Hongdong Li, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

The 3D organization of chromatin plays a fundamental role in gene regulation, cellular function, and disease mechanisms. However, current experimental techniques, such as Hi-C, remain costly and labor-intensive, limiting their application in large-scale and disease-related studies. To address this challenge, ChromNet is presented, a multi-task learning framework that integrates epigenetic signals across diverse cell types to enable high-precision prediction of chromatin architecture. By incorporating noise perturbation and auxiliary classification tasks, ChromNet improves the identification of topologically associating domains (TADs) and cell-type-specific chromatin structures, demonstrating superior generalization performance. Notably, ChromNet accurately predicts chromatin interactions in acute myeloid leukemia (AML) samples by …

A Comprehensive Overview Of Neurophysiological Correlates Of Cognitive Impairment In Amyotrophic Lateral Sclerosis, Seyyed Bahram Borgheai, Brie E. Achorn, Alyssa H. Zisk, Sarah M. Hosni, Karl E. G. Richter, Frank S. Menniti, Yalda Shahriari

Computer Science Faculty Publications

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the gradual loss of motor control, typically resulting in paralysis and death within 3 to 5 years of diagnosis. ALS shares neuropathological and genetic associations with fronto-temporal dementia (FTD), a neurodegenerative condition primarily impacting cognitive functions. These two conditions are increasingly viewed as manifestations of a single molecular disease process that affects distinct brain systems, impacting motor neuronal pathways in ALS and fronto-cortical functions in FTD. However, this simple dichotomy belies the complexity of these conditions. In particular, patients with primary motor ALS can also experience significant cognitive …

Sage: Spatially Aware Gene Selection And Dual-View Embedding Fusion For Domain Identification In Spatial Transcriptomics, Yi He, Yunpei Xu, Liqing Ding, Hong-Dong Li, Yaohang Li, Shaokai Wang

Computer Science Faculty Publications

Despite enabling high-resolution mapping of gene expression within tissues, spatial transcriptomics (ST) still faces challenges in accurately segmenting spatial domains due to complex tissue architecture and limitations of current methods. Most approaches rely on local spatial priors, lack gene-level interpretability, and fall short in capturing structure-discriminative genes or long-range functional relationships, limiting their ability to resolve biologically meaningful architectures. We present Spatially Aware Gene selection and dual-view Embedding fusion (SAGE), a unified and reproducible framework for domain identification in spatial transcriptomics that combines topic-driven gene selection with dual-view embedding fusion to address these gaps. SAGE integrates non-negative matrix factorization (NMF)-based …

Photobiomodulation Mitigates The Inhibitory Effects Of Pirfenidone On Cancer-Associated Fibroblasts And Their Pro-Tumorigenic Properties: A Cause For Concern, Nima Rastegar-Pouyani, Alireza Nasirpour, Fatemeh Javani Jouni, Hossein Vazini, Ahmad Moshaii

Electrical & Computer Engineering Faculty Publications

Cancer-associated fibroblasts (CAFs) within the tumor microenvironment highly contribute to cancer progression and poor prognosis. Recent findings introduce pirfenidone, a medication for pulmonary fibrosis, as a promising repurposed candidate for inhibiting CAFs. Moreover, photobiomodulation (PBM), or low-level laser therapy, has surfaced as a potential modality against cancer; however, its impact on CAFs is not thoroughly comprehended. The present study scrutinized the effects of PBM, pirfenidone, and PBM+pirfenidone on CAFs, and their consequent impact on cancer cells using the CAF-conditioned media. After treating CAFs with PBM at wavelengths 660 and 980 nm with/without PFD and then culturing cancer cells in the …

Covariate Selection For Rna-Seq Differential Expression Analysis With Hidden Factor Adjustment, Farzana Noorzahan, Hyeongseon Jeon, Yet Nguyen

Mathematics & Statistics Faculty Publications

In RNA-seq data analysis, a primary objective is the identification of differentially expressed genes, which are genes that exhibit varying expression levels across different conditions of interest. It is widely known that hidden factors, such as batch effects, can substantially influence the differential expression analysis. Furthermore, apart from the primary factor of interest and unforeseen artifacts, an RNA-seq experiment typically contains multiple measured covariates, some of which may significantly affect gene expression levels, while others may not. Existing methods either address the covariate selection or the unknown artifacts separately. In this study, we investigate two integrated strategies, FSR_sva and SVAall_FSR, …

Ancestry-Dependent Immunologic And Prognostic Effects Characterize The Prostate Cancer Urinary Proteome, Annie Ha, Jaron Arbet, Zhuyu Qiu, Amanda Khoo, Brian P. Main, Meinusha Govindarajan, Matthew Waas, Stanley K. Liu, O. John Semmes, Julius O. Nyalwidhe, Paul C. Boutros, Thomas Kislinger

Leroy T. Canoles Jr. Cancer Research Center Faculty Publications

Urine is an attractive biomarker analyte for non-invasive longitudinal monitoring of health and disease, particularly for diseases of the genitourinary tract, like prostate and bladder cancer. The composition of an individual's urine reflects both genetic and lifestyle characteristics that differ across geographies and populations, like diet, hydration and other socio-economic factors. While men of African ancestry have elevated prostate cancer risk, it is unclear to what extent this influences urinary biomarkers. We therefore quantified the urinary proteomes of 329 localized prostate cancer patients: 135 self-identifying as White and 194 self-identifying as Black. We identified 110 proteins that significantly differed between …

Implementing A Chatbot To Promote Hereditary Breast & Ovarian Cancer Genetic Screening In Women's Health: Identifying Barriers And Facilitators To Screening Adoption, Easton N. Wollney, Shireen Madani Sims, Luisel J. Ricks-Santi, Elizabeth Eddy, Daniel Wiesman, Carla L. Fisher

Department of Biomedical and Translational Sciences Faculty Publications

Background

To promote genetic screening among women at risk for hereditary breast and ovarian cancer (HBOC), the American College of Obstetricians and Gynecologists recommends that risk assessment be integrated into practice. Chatbots like the Genetic Information Assistant (Gia®) are increasingly implemented to expand access to hereditary genetic screening. Factors that impact chatbot implementation for HBOC risk screening and women's uptake are not fully realized. To refine implementation strategies prior to full scale implementation, we sought to identify women's perceived facilitators/barriers to adopting Gia screening in a rural population within a large healthcare system in the southern United States.

Methods

We …

Epigenetic Regulation In Fibrosis, Qingping Wei, Xiaoru Hu, Yan Sanders

Department of Biomedical and Translational Sciences Faculty Publications

[Introduction] Fibrosis is one of the pathological conditions underlying the progression of numerous chronic diseases, and it contributes substantially to morbidity and mortality worldwide. Increasing amounts of evidence indicate that epigenetic mechanisms—including DNA methylation, histone modifications, RNA modifications, and non-coding RNAs—play pivotal roles in epithelial cell injury and maladaptive tissue repair, inflammatory cell and fibroblast activation, and extracellular matrix remodeling and accumulation. Compared to genetic alterations, epigenetic changes are relatively reversible, positioning them as promising therapeutic targets. The articles collected in this Research Topic highlight recent advances in understanding how epigenetic regulation shapes fibrotic processes across multiple organ systems and …

Late Diagnosis Of Klinefelter Syndrome: Overcoming Phenotypic Variability And Diagnostic Oversights, Amna Kamran, Chinelo Okigbo

Department of Medicine Faculty Publications

We report a case of Klinefelter syndrome (KS) diagnosed in adulthood, emphasizing the impact of phenotypic variability and the declining reliance on physical examination in delayed recognition. A 27-year-old male with obesity, low libido, and biochemical and clinical primary hypogonadism was found to have 47, XXY karyotype, consistent with KS. His hypogonadism was initially attributed to obesity and overlooked, despite classic signs of a micropenis and small testes. The case highlights the importance of physical examination, comprehensive history, and clinician awareness in diagnosing KS, particularly in atypical presentations. KS is associated with increased risks of osteoporosis, cardiovascular disease, and psychosocial …

An Ewas Of Dementia Biomarkers And Their Associations With Age, African Ancestry, And Ptsd, Mark W. Miller, Erika J. Wolf, Xiang Zhao, Mark W. Logue, Sage E. Hawn

Psychology Faculty Publications

Background

Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.

Methods

Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which …

Refinement Of Saliva Microrna Biomarkers For Sports-Related Concussion, Steven D. Hicks, Cayce Onks, Raymond Y. Kim, Kevin J. Kim, Kevin J. Zhen, Jayson Loeffert, Andrea C. Loeffert, Robert P. Olympia, Gregory Fedorchak, Samantha Devita, Zofia Gagnon, Callan Mcloughlin, Miguel M. Madeira, Scott L. Zuckerman, Timothy Lee, Matthew Heller, Chuck Monteith, Thomas R. Campbell, Christopher Neville, Elise Fengler, Michael N. Dretsch

Rehabilitation Sciences Faculty Publications

Purpose

Recognizing sport-related concussion (SRC) is challenging and relies heavily on subjective symptom reports. An objective, biological marker could improve recognition and understanding of SRC. There is emerging evidence that salivary micro-ribonucleic acids (miRNAs) may serve as biomarkers of concussion; however, it remains unclear whether concussion-related miRNAs are impacted by exercise. We sought to determine whether 40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports. Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.

Methods

This case-control study harmonized …

Plasmonic-Based Biosensor For The Early Diagnosis Of Prostate Cancer, Thakshila Liyanage, Bayan Alharbi, Linh Quan, Aurora Esquela-Kerscher, Gymama Slaughter

Bioelectrics Publications

A tapered optical fiber (TOF) plasmonic biosensor was fabricated and used for the sensitive detection of a panel of microRNAs (miRNAs) in human serum obtained from noncancer and prostate cancer (PCa) patients. Oncogenic and tumor suppressor miRNAs let7a, let-7c, miR-200b, miR-141, and miR-21 were tested as predictive cancer biomarkers since multianalyte detection minimizes false-positive and false-negative rates and establishes a strong foundation for early PCa diagnosis. The biosensing platform integrates metallic gold triangular nanoprisms (AuTNPs) laminated on the TOF to excite surface plasmon waves in the supporting metallic layer and enhance the evanescent mode of the fiber surface. …

Robust Meta-Analysis For Large-Scale Genomic Experiments Based On An Empirical Approach, Sinjini Sikdar

Mathematics & Statistics Faculty Publications

BACKGROUND: Recent high-throughput technologies have opened avenues for simultaneous analyses of thousands of genes. With the availability of a multitude of public databases, one can easily access multiple genomic study results where each study comprises of significance testing results of thousands of genes. Researchers currently tend to combine this genomic information from these multiple studies in the form of a meta-analysis. As the number of genes involved is very large, the classical meta-analysis approaches need to be updated to acknowledge this large-scale aspect of the data.

METHODS: In this article, we discuss how application of standard theoretical null distributional assumptions …

Reduction Of Plasmid Vector Backbone Length Enhances Reporter Gene Expression, Carly Boye, Sezgi Arpag, Michael Francis, Scott Declemente, Aislin West, Richard Heller, Anna Bulysheva

Electrical & Computer Engineering Faculty Publications

Gene therapy has a wide range of applications for various types of pathologies. Viral methods of gene delivery provide high levels of gene expression but have various safety concerns. Non-viral methods are largely known to provide lower levels of expression. We aim to address this issue by using plasmid DNA with smaller backbones to increase gene expression levels when delivered using non-viral methods. In this study we compare gene expression levels between two vectors with firefly luciferase encoding gene insert using liposome complexes and gene electrotransfer as delivery methods. A 2-fold reduction in plasmid vector backbone size, disproportionately enhanced gene …

A Novel Dimensionality Reduction Approach To Improve Microarray Data Classification, Mohammed Hasim, Ismail El Mouden, Mounir Ouzir, Hicham Moutachaouik, Mustapha Hain

Department of Medicine Faculty Publications

Cancer tumor prediction and diagnosis at an early stage has become a necessity in cancer research, as it provides an increase in the treatment success chances. Recently, DNA microarray technology became a powerful tool for cancer identification, that can analyze the expression level of a different and huge number of genes simultaneously. In microarray data, the large genes number versus a few records may affect the prediction performance. In order to handle this "curse of dimensionality” constraint of microarray dataset while improving the cancer identification performance, a dimensional reduction phase is necessary. In this paper, we proposed a framework that …

Gene Selection For Cancer Classification: A New Hybrid Filter-C5.0 Approach For Breast Cancer Risk Prediction, Mohammed Hamim, Ismail El Moudden, Hicham Moutachaouik, Mustapha Hain

Department of Medicine Faculty Publications

Despite the significant progress made in data mining technologies in recent years, breast cancer risk prediction and diagnosis at an early stage using DNA microarray technology still a real challenging task. This challenge comes especially from the high-dimensionality in gene expression data, i.e., an enormous number of genes versus a few tens of subjects (samples). To overcome this problem of data imbalance, a gene selection phase becomes a crucial step for gene expression data analysis. This study proposes a new Decision Tree model-based attributes (genes) selection strategy, which incorporates two stages: fisher-score-based filter technique and the gene selection ability of …

Monopolar Gene Electrotransfer Enhances Plasmid Dna Delivery To Skin, Anna Bulysheva, Loree Heller, Michael Francis, Frency Varghese, Carly Boye, Richard Heller

Electrical & Computer Engineering Faculty Publications

A novel monopolar electroporation system and methodologies were developed for in vivo electroporation intended for potential clinical applications such as gene therapy. We hypothesized that an asymmetric anode/cathode electrode applicator geometry could produce favorable electric fields for electroporation, without the typical drawback associated with traditional needle and parallel plate geometries. Three monopolar electrode applicator prototypes were built and tested for gene delivery of reporter genes to the skin in a guinea pig model. Gene expression was evaluated in terms of kinetics over time and expression distribution within the treatment site. Different pulsing parameters, including pulse amplitude, pulse duration, and pulse …